Flashcards in Prader-Willi (Dr. Elias - L2) Deck (17)
What is a common finding, during pregnancy, if a fetus has PW?
What is notable immediately at birth?
decreased fetal movements
dysmorphic (unusual facial features)
almond shaped eyes
cryptorchidism (undescended testicles)
In a child with PW what is likely to be seen on a FISH test?
Why might this finding not always occur in a PW diagnosis?
likely: del(15)(q11-q13) deletion on long arm of paternal chrom. 15
also possible: uniparental disomy; two copies of chrom 15 from mom, none from dad
Due to the hypotonia seen in PW infants, what are some common complications?
may need a gastrostomy tube
What is strabismus and nystagmus?
strabismus = lazy eye
nystagmus = jiggly eye
What is the hallmark symptom that develops in a child with PW around pre-school age?
--> weight gain
What is a common early treatment for PW and what symptom is a contraindication for this treatment?
contraindicated if the child has obstructive sleep apnea.
Do patients with PW have intellectual disabilities?
Yes, mild to moderate.
Explain briefly how a FISH would pick up a deletion on chromosome 15 indicating PW
A chromosome 15 probe labels the chromosome 15.
A SNRPN probe is added and if it does not attach to one of the chr. 15's that indicates a deletion of the region associated with PW.
5'UTR of the SNRPN gene is an imprinting center and will be methylated (silenced) in uniparental disomy cases of PW.
What other disorder can be caused by a deletion on the long arm of chromosome 15?
Angleman's syndrome. deletion on the maternal allele.
How could you distinguish whether PW syndrome is caused by a deletion on the parental chrm 15 or UPD?
UPD would be indicated by two chromosome 15's both with the maternal imprinting (methylation) pattern.
This can be from a methylation (imprinting) error on the father's chr. 15 or it can be from two maternal chr. 15's and no paternal chr. 15
List some common medical issues seen in PW patients.
Eyes: strabismus, nystagmus
Respiratory: obstructive sleep apnea (which contraindicates use of GH to treat)
Developmentally: mild-moderate cognitive disabilities; behavioral issues; picking & scratching disorders = skin issues
What neurotransmitter on the b3 locus of chrom. 15 is thought to be affected in pts with Autism?
encoding for certain GABA receptors located in the 15q11-13 region affected in maternal deletions
Inverted, duplicated isodicentric 15q
phenotype is hypotonia, severe intellectual disabilities, autism and seizures
Discuss the genetic mechanisms leading to Angelman's syndrome
1. deletion in 15q11-13 (PWSAS region) on maternal allele
2. UBE 3A mutation on maternal allele
3. Paternal UPD (missing mother's copy completely)
4. Imprinting defect (maternal allele is imprinted with paternal pattern; "looks" like paternal UPD)
Gene associated with Prader-Willi syndrome?
On chromosome 15, gene is SNORD116
Gene associated with Angleman's syndrome?
UBE3A on chromosome 15